Proteostasis and Ribostasis Impairment as Common Cell Death Mechanisms in Neurodegenerative Diseases DOI Creative Commons
Su Min Lim, Minyeop Nahm, Seung Hyun Kim

et al.

Journal of Clinical Neurology, Journal Year: 2023, Volume and Issue: 19(2), P. 101 - 101

Published: Jan. 1, 2023

The cellular homeostasis of proteins (proteostasis) and RNA metabolism (ribostasis) are essential for maintaining both the structure function brain. However, aging, stress conditions, genetic contributions cause disturbances in proteostasis ribostasis that lead to protein misfolding, insoluble aggregate deposition, abnormal ribonucleoprotein granule dynamics. In addition neurons being primarily postmitotic, nondividing cells, they more susceptible persistent accumulation aggregates. Indeed, defects associated with failure maintain common pathogenic components age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis. Furthermore, neuronal deposition misfolded aggregated can increased toxicity impaired physiological function, which dysfunction cell death. There is recent evidence irreversible liquid-liquid phase separation (LLPS) responsible formation disease-related proteins, tau, α-synuclein, RNA-binding transactive response DNA-binding 43, fused sarcoma, heterogeneous nuclear A1. Investigations LLPS its control therefore suggest chaperone/disaggregase, reverse aggregation, valuable therapeutic targets effective treatments neurological diseases. Here we review discuss studies highlight importance understanding death mechanisms

Language: Английский

RNA-binding proteins and cancer metastasis DOI
Shengjie Wang,

Zelong Sun,

Zhe Lei

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 748 - 768

Published: March 23, 2022

Language: Английский

Citations

99
Alternative splicing and related RNA binding proteins in human health and disease DOI Creative Commons

Yining Tao,

Qi Zhang, Haoyu Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 2, 2024

Abstract Alternative splicing (AS) serves as a pivotal mechanism in transcriptional regulation, engendering transcript diversity, and modifications protein structure functionality. Across varying tissues, developmental stages, or under specific conditions, AS gives rise to distinct splice isoforms. This implies that these isoforms possess unique temporal spatial roles, thereby associating with standard biological activities diseases. Among these, AS-related RNA-binding proteins (RBPs) play an instrumental role regulating alternative events. Under physiological the diversity of mediated by influences structure, function, interaction, localization proteins, participating differentiation development array tissues organs. pathological alterations are linked various diseases, particularly cancer. These changes can lead gene patterns, culminating loss For instance, cancer, abnormalities RBPs may result aberrant expression cancer-associated genes, promoting onset progression tumors. also associated numerous neurodegenerative diseases autoimmune Consequently, study across different holds significant value. review provides detailed account recent advancements tissue which aids deepening understanding complexity offers new insights methodologies for precision medicine.

Language: Английский

Citations

75
Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain DOI Creative Commons
Nicole Scott‐Hewitt, Matthew Mahoney, Youtong Huang

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4193 - 4212.e24

Published: June 27, 2024

Language: Английский

Citations

19
The Rab5 effector FERRY links early endosomes with mRNA localization DOI Creative Commons
Jan S. Schuhmacher, Susanne tom Dieck, Savvas Christoforidis

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(11), P. 1839 - 1855.e13

Published: June 1, 2023

Localized translation is vital to polarized cells and requires precise robust distribution of different mRNAs ribosomes across the cell. However, underlying molecular mechanisms are poorly understood important players lacking. Here, we discovered a Rab5 effector, five-subunit endosomal RNA/ribosome intermediary (FERRY) complex, that recruits early endosomes through direct mRNA-interaction. FERRY displays preferential binding certain groups transcripts, including encoding mitochondrial proteins. Deletion subunits reduces localization transcripts in has significant impact on mRNA levels. Clinical studies show genetic disruption causes severe brain damage. We found that, neurons, co-localizes with endosomes, loaded FERRY-positive close proximity mitochondria. thus transforms into carriers plays key role regulating transport.

Language: Английский

Citations

36
RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific DOI Creative Commons

Debashish Ray,

Kaitlin U. Laverty,

Arttu Jolma

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 31, 2023

Abstract Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)—proteins that associate with RNA but lack known domains (RBDs). The vast majority ucRBPs have uncharacterized specificities. We analyzed 492 human for intrinsic in vitro and identified 23 bind specific sequences. Most (17/23), including 8 ribosomal proteins, were previously associated RNA-related function. the RBDs responsible sequence-specific several surveyed whether corresponding from homologous also display sequence specificity. CCHC-zf seven recognized motifs, indicating this is a major class RBD. For Nudix, HABP4, TPR, RanBP2-zf, L7Ae domains, however, only isolated members or closely related homologs yielded consistent as derived specificity most striking, we suggest many may function analogously chromatin factors, which often efficiently DNA, presumably via indirect recruitment. Finally, show tend be highly abundant their identification interactome capture studies could result weak nonspecific interactions RNA.

Language: Английский

Citations

30
The RNA-binding protein landscapes differ between mammalian organs and cultured cells DOI Creative Commons
Joel I. Perez-Perri,

Dunja Ferring–Appel,

Ina Huppertz

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 12, 2023

Abstract System-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo enhanced RNA interactome capture (eRIC) characterize three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) these had formerly not been identified cells, with 100 being metabolic enzymes. Remarkably, RBP activity differs between independent abundance, suggesting organ-specific levels control. Similarly, identify systematic differences binding animal and pervasive enzymes intermediary metabolism points tightly knit connections gene expression metabolism, displays particular enrichment for that use nucleotide cofactors. We generically applicable refinement eRIC technology provide instructive resource intact organs, including brain.

Language: Английский

Citations

29
RNA granules in neuronal plasticity and disease DOI Open Access

Karl E. Bauer,

Bruna R. de Queiroz, Michael Kiebler

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(7), P. 525 - 538

Published: May 16, 2023

Language: Английский

Citations

28
Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine DOI Creative Commons
Macarena Las Heras,

Benjamín Szenfeld,

Rami A. Ballout

et al.

npj Genomic Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 11, 2023

Niemann-Pick type C (NPC) disease is a lysosomal storage (LSD) characterized by the buildup of endo-lysosomal cholesterol and glycosphingolipids due to loss function mutations in NPC1 NPC2 genes. NPC patients can present with broad phenotypic spectrum, differences at age onset, rate progression, severity, organs involved, effects on central nervous system, even response pharmacological treatments. This article reviews variation discusses its possible causes, such as remaining defective protein, modifier genes, sex, environmental cues, splicing factors, among others. We propose that these factors should be considered when designing or repurposing treatments for this disease. Despite seeming complexity, proposition not far-fetched, considering expanding interest precision medicine easier access multi-omics technologies.

Language: Английский

Citations

25
Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis DOI Creative Commons
Mirolyuba Ilieva

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1063 - 1063

Published: June 19, 2024

Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, focus has shifted toward intricate world non-coding RNAs (ncRNAs), class RNA molecules that do not encode proteins but play pivotal roles in gene regulation cellular processes. This review explores emerging significance ncRNAs context neurological disorders, shedding light on diverse functions regulatory mechanisms. The dysregulation various ncRNAs, including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), been implicated pathophysiology conditions such as Alzheimer’s disease, Parkinson’s schizophrenia, mood disorders. delves into specific these modulating key processes, synaptic plasticity, neuroinflammation, apoptosis, providing nuanced impact disease progression. Furthermore, it discusses potential diagnostic therapeutic implications targeting identification ncRNA signatures holds promise for development novel biomarkers early detection, while manipulation expression offers innovative avenues. Challenges future directions field are also considered, highlighting need continued research unravel complexities ncRNA-mediated networks aims provide overview current state knowledge stimulate further exploration fascinating realm brain’s landscape.

Language: Английский

Citations

12
Spatiotemporally resolved transcriptomics reveals the cellular dynamics of human retinal development DOI Creative Commons
Jinglong Zhang, Jiao Wang,

Qiongjie Zhou

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

The morphogenesis and cellular interactions in developing retina are incompletely characterized. full understanding needs a precise mapping of the gene expression with single-cell spatial resolution. Here, we present transcriptomic (ST) resource for human at six developmental stages. Combining data enables characterization cell-type-specific profiles distinct anatomical regions each stage, highlighting spatiotemporal dynamics composition during retinal development. All ST spots catalogued into consensus domains, which further associated to their specific signatures biological functions neuron eye We prioritize set critical regulatory genes transitions domains Differentially expressed from different diseases, indicating relevance clinical significance spatially defined expression. Finally, reconstruct communication networks, highlight ligand-receptor Overall, our study reports development, provides rich future studies on retinogenesis.

Language: Английский

Citations

1